Background Allergen-specific immunotherapy (allergen-SIT) is the only treatment directed at the cause of IgE-mediated allergic diseases. However, there is controversy over the use of SIT for patients ...with atopic dermatitis. Objective We performed a systematic review and meta-analysis to assess the efficacy of SIT for patients with atopic dermatitis. Methods We performed manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane databases (through December 10, 2012) for randomized controlled trials that compared SIT with placebo for patients with atopic dermatitis. The outcome of interest was a dichotomous variable, in terms of treatment success; a meta-analysis was performed by using a random-effects analysis. Subgroup analyses were carried out to evaluate the effects of long-term treatment (more than 1 year), SIT for severe atopic dermatitis, SIT for children, and subcutaneous and sublingual administration of immunotherapy. Results We analyzed 8 randomized controlled trials that comprised a total of 385 subjects. We found that SIT has a significant positive effect on atopic dermatitis (odds ratio OR, 5.35; 95% CI, 1.61-17.77; number needed to treat, 3; 95% CI, 2-9). SIT also showed significant efficacy in long-term treatment (OR, 6.42; 95% CI, 1.50-27.52) for patients with severe atopic dermatitis (OR, 3.13; 95% CI, 1.31-7.48), and when administered subcutaneously (OR, 4.27; 95% CI, 1.36-13.39). Conclusions A meta-analysis provides moderate-level evidence for the efficacy of SIT against atopic dermatitis. However, these findings are based on an analysis of a small number of randomized controlled trials, with considerable heterogeneity among trials.
This brief presents an 8-to-16-Gb/s referenceless receiver with a stochastic continuous-time linear equalizer (CTLE) adaptation. The proposed stochastic CTLE gain selector (SCGS) achieves a maximum ...horizontal eye margin and avoids sub-optimal settling by utilizing sequential edge and data samples. The proposed SCGS detects the optimum CTLE coefficient with the weighted summation of the histograms obtained under various data patterns and channel conditions. The stochastic CTLE adaptation shares the deserialized edge and data samples used for the CDR. Therefore, it does not require additional hardware in the analog domain, achieving low power consumption. The golden weight of the SCGS is obtained through an epsilon-constraint weight searching algorithm. A prototype chip fabricated in 28-nm CMOS technology occupies an active area of 0.029 mm2. The measured CTLE adaptation behavior shows that the maximum eye width is achieved with the proposed SCGS. The prototype chip achieves BER over a channel with 14-dB loss at 8 GHz and consumes 17.7 mW at 16 Gb/s, exhibiting a power efficiency of 1.1 pJ/b.
What are the apparent research and methodological trends in PAR's content over the past decade? From the perspective of the journal's 70-year history, with its aim to "mesh" practitioner and academic ...knowledge creation, topical coverage since 2000 reflects striking continuity, emphasizing many of the "bread and butter" administrative issues such as planning, human resources, budgeting, and public management. A marked increase in coverage is apparent in the application of more sophisticated quantitative statistical methodology, as well as in the number of female authors, while the number of practitioner authors declined sharply. Throughout the first turbulent decade of the twenty-first century, three intellectual themes stood out: evaluations of New Public Management, connections between practitioners and academicians, and responsiveness to immediate social, economic, and political challenges. Given the constant demand for usable knowledge, scholars seem to have marginalized attention to the historical context and epistemologicalfoundations of the study. The central challenge in the years ahead will be to effectively use research methods in response to the big questions of government and society that defy measurement.
Disuse muscle atrophy is characterized by a decrease in muscle mass and strength and an increase in glycolytic muscle fiber type. Although Schisandra chinensis extract has beneficial effects on ...muscle atrophy induced by various conditions (e.g., dexamethasone and aging), the effect of gomisin G, a lignan component of S. chinensis, on disuse muscle atrophy is unclear. Here, we induced disuse muscle atrophy through wire immobilization of the hind legs in mice followed by the oral administration of gomisin G. The cross-sectional area and muscle strength in disuse muscle atrophic mice were increased by gomisin G; however, the total muscle mass did not increase. Gomisin G decreased the expression of muscle atrophic factors (myostatin, atrogin-1, and MuRF1) but increased the expression of protein synthesis factors (mTOR and 4E-BP1). In H2O2-treated C2C12 myotubes, the level of puromycin incorporation (as a marker of protein synthesis) gradually increased in a dose-dependent manner by gomisin G. Furthermore, gomisin G induced a muscle fiber switch from fast-type glycolytic fibers (type 2B) to slow-type oxidative fibers (type I, 2A) in the gastrocnemius (GA) muscle as proved a decrease in the expression of TnI-FS and an increase in the expression of TnI-SS. Gomisin G increased mitochondrial DNA content and ATP levels in the GA muscle and COX activity in H2O2-treated C2C12 myotubes, improving mitochondrial function. Mechanistically, mitochondrial biogenesis is regulated by gomisin G via the Sirt 1/PGC-1α signaling pathway, targeting NRF1 and TFAM. These data suggest that gomisin G has a potential therapeutic effect on disuse muscle atrophy.
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•Gomisin G improves grip strength in disuse muscle atrophic mice.•Gomisin G increases muscle synthesis rate in H2O2-treated C2C12 myotubes.•Gomisin G increases slow-type oxidative fiber contents in muscle of disuse mice.•Gomisin G induces mitochondrial biogenesis via the Sirt 1/PGC-1α signaling pathway.
The coronavirus disease 2019 (COVID-19) pandemic is being overcome by widespread inoculation with various COVID-19 vaccines, but concerns about the safety of the vaccines are a major hurdle to ...widespread vaccination. We report the first case of adult-onset Still's disease (AOSD) developing in a 36-year-old, previously healthy woman after the first dose of BNT162b2 mRNA COVID-19 vaccine (Pfizer). She visited our hospital due to high spiking fever and sore throat that developed 10 days after vaccination. Based on thorough investigations and changes in symptoms and signs after admission, she was diagnosed with AOSD and treated with high dose steroids and tocilizumab. This report suggests the possibility that AOSD could be triggered by COVID-19 vaccines through activation of the innate immune system.
Purpose
This study aimed to compare the renoprotective effect between febuxostat and allopurinol in hyperuricemic patients with chronic kidney disease (CKD), about which limited data are available.
...Methods
141 patients with stage 3 CKD and hyperuricemia were followed from June 2005 to April 2018. Thirty patients received febuxostat, 40 allopurinol and 71 conventional CKD management only (control group). We compared the mean serum uric acid levels, estimated glomerular filtration rate (eGFR) changes over time and renal survival time free from predefined renal disease progression among these 3 groups.
Results
Overall, mean age was 62.6 ± 13.3 years, baseline eGFR 42.1 ± 8.8 mL/min/1.73 m
2
, and serum uric acid 8.6 ± 1.5 mg/dL without intergroup difference. During the observation period (55.9 ± 31.8 months), febuxostat group, compared to both allopurinol and control group, had significantly lower mean serum uric acid levels (5.7 ± 1.0 vs. 7.1 ± 1.2 vs. 8.0 ± 0.8 mg/dL,
p
< 0.001) and maintained significantly higher mean eGFR values consistently for 4 years. Febuxostat group had significantly longer renal survival time free from renal disease progression than allopurinol and control group (87.7 (95% CI 71.2–104.2) vs. 77.6 (95% CI 60.2–94.9) vs. 48.7 (95% CI 39.3–58.1) months, respectively,
p
< 0.001). Cox proportional hazard model analysis adjusting for potent confounders revealed that febuxostat, with control group as reference, significantly reduced the risk of renal disease progression by 74.3% (hazard ratio 0.257 (95% CI 0.072–0.912),
p
= 0.036), while allopurinol showed insignificant result.
Conclusions
Febuxostat seems to reduce serum uric acid level and to retard renal disease progression more effectively than allopurinol in hyperuricemic patients with CKD.
Despite large-scale financial support of the government, there is increasing criticism about the inefficiency of public R&D investment that fails to lead directly to technological innovation of ...technology-based start-ups. This paper analyzes the factors that influence technological innovation in Korean technology-based start-ups based on the resource-based view (RBV). The empirical analysis combines ordinary least squares and ordered probit analysis of data collected from 248 technology-based start-ups in Korea. The analysis results statistically confirm the effects of technological capabilities and entrepreneurship on technological innovation. First, a start-up's technological capabilities measured by patents and technological competitiveness have significant positive effects on technological innovation, while the effect of having an in-house R&D department for technological innovation is not significant. Second, entrepreneurship has a significant positive effect on the technological innovation of a start-up, and this positive effect has a moderating effect that further promotes the positive effect of technological competitiveness on technological innovation.
In compliance with green chemistry, metallic nanoparticles can be biogenically synthesized using plant extracts. Herein, three different deep eutectic solvents (DESs) were used instead of water to ...prepare green tea extracts (GTEs). The resultant DES-based GTEs exerted different beneficial effects on the biosynthesis of silver nanoparticles. Compared with the water-based GTE (W-GTE), the DES-based GTEs contained higher levels of catechins (up to 235% more) that are natural reducing and capping agents and showed higher synthesis efficiency. In particular, two DESs, which consist of glycerol and betaine with a common urea molecule and are designated as GU and BU, respectively, could produce silver nanoparticles with superior properties to water. Specifically, GU- and BU-GTE-based silver nanoparticles showed uniformly reduced sizes, 39.12 (±5.33) nm and 43.11 (±6.42) nm, respectively and homogenous face-centered cubic crystallinity. DESs added to W-GTEs lead to synthesis of silver nanoparticles with improved dispersion. The DES-GTE-based silver nanoparticles at 60 μg/mL displayed in vitro anti-cancer activity comparable to doxorubicin at 12.5 μg/mL. These results suggest that the tested DESs could serve as efficient extraction solvents for phytochemicals as well as effective surface modifiers without posing adverse effects for subsequent applications of the synthesized nanoparticles. The favorable effects of GU and BU were found to partially involve ammonia, which was formed during DES preparation at high temperatures (≥80 °C). This study shows that DESs can promote the biogenic synthesis of silver nanoparticles by playing diverse roles depending on the unique properties of the DESs and their constituents.
•DES-based green tea extracts were used to synthesize AgNPs for the first time.•DESs exert constructive effects on synthesis efficiency, particle size, and dispersion.•DESs can efficiently extract phytochemicals (reducing and end capping agents).•DESs can also serve as effective surface modifiers of AgNPs.•Ammonia unintentionally produced in DESs can affect the AgNP biosynthesis.
Tyrosinase is a copper-binding enzyme involved in melanin biosynthesis. However, the detailed structure of human tyrosinase has not yet been solved, along with the identification of the key sites ...responsible for its catalytic activity. We used site-directed mutagenesis to identify the residues critical for the copper binding of human tyrosinase. Seven histidine mutants in the two copper-binding sites were generated, and catalytic activities were characterised. The tyrosine hydroxylase activities of the CuA site mutants were approximately 50% lower than those of the wild-type tyrosinase, while the dopa oxidation activities of the mutants were not significantly different from that of wild-type tyrosinase. By contrast, mutations at CuB significantly decreased both tyrosine hydroxylation and dopa oxidation activities, confirming that the catalytic sites for these two activities are at least partially distinct. These findings provide a useful resource for further structural determination and development of tyrosinase inhibitors in the cosmetic and pharmaceutical industries.
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